Phase III Study of Hemospan® to Prevent Hypotension in Hip Arthroplasty

NCT ID: NCT00421200

Last Updated: 2013-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 375 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2008-06-30

Brief Summary

The purpose of this study is to determine whether Hemospan is superior to Voluven for preventing hypotensive episodes during the perioperative period (from induction of spinal anesthesia until 6 hours after skin closure), and for reducing the incidence of operative and postoperative complications including organ dysfunction and failure until follow-up at one month following surgery. An independent Data Safety Monitoring Board (DSMB) will periodically evaluate the safety data collected during this trial.

Detailed Description

Hemospan is a novel hemoglobin-based oxygen carrier developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. As a result of its molecular size and oxygen binding characteristics, Hemospan selectively off-loads oxygen in tissues predisposed to low oxygen tension. Preclinical evidence suggests that Hemospan provides rapid and effective plasma expansion and tissue perfusion, and that the properties of Hemospan target oxygen release in the microcirculation.

Spinal anesthesia is the preferred choice for hip arthroplasty procedures in elderly patients, but is associated with a functional hypovolemia due to loss of vascular tone that frequently causes acute hypotensive episodes. Hypotension represents a surrogate marker of hypovolemia that may be further exacerbated by surgical bleeding, which can result in decreased cardiac output, insufficient perfusion and inadequate tissue oxygenation. Ischemia resulting from hypotension can adversely affect vital organ function and may result in complications and postoperative morbidity. As the population ages and more patients become candidates for orthopedic reconstruction or joint replacement surgery, the number of patients at risk is increasing. The ideal IV solution for preventing hypovolemia-associated hypotension and improving hemodynamic stability would be an effective plasma expander that promotes tissue perfusion and delivers oxygen to ischemic or marginally hypoxic tissue.

Preclinical animal studies have shown that Hemospan may be well-suited to this application and may even be better than blood in some situations. Data from Sangart's Phase II orthopedic surgery study (No. 6055), published recently by Olofsson et al. (Anesthesiology 2006; 105(6): 1153-63) support the safety and potential benefit of Hemospan for preventing hypotension in orthopedic surgery patients undergoing hip replacement surgery under spinal anesthesia.

Conditions

Hypotension; Ischemia

Keywords

Hip arthroplasty; Anesthesia, spinal; Hypotension; Ischemia; Blood substitutes; Plasma expanders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Hemospan (MP4OX)

4.3 g/dL MalPEG-Hb solution

Group Type: EXPERIMENTAL

Hemospan (MP4OX)

Intervention Type: DRUG

250 ml unit dose, up to 500 mL total dose, as needed at protocol-defined dosing triggers

Control

Voluven (HES 130/0.4)

Group Type: ACTIVE_COMPARATOR

Voluven (HES 130/0.4)

Intervention Type: DRUG

250 ml unit dose, up to 500 mL total dose, as needed at protocol-defined dosing triggers

Interventions

Hemospan (MP4OX)

250 ml unit dose, up to 500 mL total dose, as needed at protocol-defined dosing triggers

Intervention Type: DRUG

Voluven (HES 130/0.4)

250 ml unit dose, up to 500 mL total dose, as needed at protocol-defined dosing triggers

Intervention Type: DRUG

Other Intervention Names

MP4OX solution; 4.3 g/dL MalPEG-Hb; PEGylated Hb; 6% hetastarch solution; 6% HES 130/0.4

Eligibility Criteria

Inclusion Criteria

• Patients scheduled to undergo elective primary hip arthroplasty (based on an osteoarthritis diagnosis) under spinal anesthesia
• Adult male or female (surgically sterile or post-menopausal), aged 50 years or older
• American Society of Anesthesiology (ASA) Class II or III
• Physical examination, laboratory status, vital signs, and ECG within acceptable limits for the planned surgery, as judged by the investigator
• Have been given written and verbal information by the investigator about Hemospan and the protocol, and have had the opportunity to ask questions about the study
• Patients must sign an Informed Consent form that has been reviewed and approved by the independent Ethics Committee

Exclusion Criteria

• Hip fracture patients and nail/pin extraction procedures
• Clinical evidence of uncontrolled cardiovascular, infectious, psychiatric, metabolic or systemic disorders including diabetes and rheumatoid arthritis
• Evidence of significant hypertension with SBP >180 mmHg, or a difference in SBP obtained in each arm that is >15 mmHg (measured in the supine position in both arms, at screening)
• Recent history or evidence of MI or stroke (within 6 months)
• Known alcohol or drug dependency
• Currently taking oral anti-coagulant therapy; except for low-dose aspirin (acetylsalicylic acid), <200 mg/day
• History of coagulopathy
• Involved in any investigational drug or device trial within 30 days prior to this study
• Professional or ancillary personnel involved with this study

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sangart

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christina I. Olofsson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

Univ. Ziekenhuis Antwerp

Antwerp, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

ZOL Campus Sint-Jan

Genk, , Belgium

AZ St. Lucas Hospital

Ghent, , Belgium

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Oblastni nemocnice Kladno

Kladno, , Czechia

Fakultni nemocnice Motol

Prague, , Czechia

Fakultni nemocnice Na Bulovce

Prague, , Czechia

Sint Maartenskliniek

Nijmegen, , Netherlands

Universitair Medisch Centrum St. Radboud

Nijmegen, , Netherlands

SPSK nr 4, Klinika Ortopedii, Traumatologii i Rehabilitacji AM

Lublin, , Poland

SP Wojewódzki Szpital Chirurgii Urazowej

Piekary Śląskie, , Poland

Wojewódzki Szpital Specjalistyczny nr 5

Sosnowiec, , Poland

SK Dzieciątka Jezus

Warsaw, , Poland

Skaraborg Hospital

Skövde, , Sweden

Karolinska Hospital

Stockholm, , Sweden

S:t Görans Hospital

Stockholm, , Sweden

Univ. Hospital - Queen's Medical Center

Nottingham, , United Kingdom

Countries

Belgium; Czechia; Netherlands; Poland; Sweden; United Kingdom

References

Bjorkholm M, Fagrell B, Przybelski R, Winslow N, Young M, Winslow RM. A phase I single blind clinical trial of a new oxygen transport agent (MP4), human hemoglobin modified with maleimide-activated polyethylene glycol. Haematologica. 2005 Apr;90(4):505-15.

Reference Type: BACKGROUND

PMID: 15820947 (View on PubMed)

Cabrales P, Tsai AG, Winslow RM, Intaglietta M. Effects of extreme hemodilution with hemoglobin-based O2 carriers on microvascular pressure. Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2146-53. doi: 10.1152/ajpheart.00749.2004. Epub 2005 Jan 6.

Reference Type: BACKGROUND

PMID: 15637119 (View on PubMed)

Young MA, Riddez L, Kjellstrom BT, Bursell J, Winslow F, Lohman J, Winslow RM. MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit Care Med. 2005 Aug;33(8):1794-804. doi: 10.1097/01.ccm.0000172648.55309.13.

Reference Type: BACKGROUND

PMID: 16096458 (View on PubMed)

Tsai AG, Cabrales P, Manjula BN, Acharya SA, Winslow RM, Intaglietta M. Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers. Blood. 2006 Nov 15;108(10):3603-10. doi: 10.1182/blood-2006-02-005272. Epub 2006 Jul 20.

Reference Type: BACKGROUND

PMID: 16857991 (View on PubMed)

Winslow RM. Current status of oxygen carriers ('blood substitutes'): 2006. Vox Sang. 2006 Aug;91(2):102-10. doi: 10.1111/j.1423-0410.2006.00789.x.

Reference Type: BACKGROUND

PMID: 16907870 (View on PubMed)

Olofsson C, Ahl T, Johansson T, Larsson S, Nellgard P, Ponzer S, Fagrell B, Przybelski R, Keipert P, Winslow N, Winslow RM. A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery. Anesthesiology. 2006 Dec;105(6):1153-63. doi: 10.1097/00000542-200612000-00015.

Reference Type: BACKGROUND

PMID: 17122578 (View on PubMed)

Winslow RM. Red cell substitutes. Semin Hematol. 2007 Jan;44(1):51-9. doi: 10.1053/j.seminhematol.2006.09.013.

Reference Type: BACKGROUND

PMID: 17198847 (View on PubMed)

Olofsson CI, Gorecki AZ, Dirksen R, Kofranek I, Majewski JA, Mazurkiewicz T, Jahoda D, Fagrell B, Keipert PE, Hardiman YJ, Levy H; Study 6084 Clinical Investigators. Evaluation of MP4OX for prevention of perioperative hypotension in patients undergoing primary hip arthroplasty with spinal anesthesia: a randomized, double-blind, multicenter study. Anesthesiology. 2011 May;114(5):1048-63. doi: 10.1097/ALN.0b013e318215e198.

Reference Type: RESULT

PMID: 21455059 (View on PubMed)

Related Links

http://www.sangart.com

Click here for more information about Sangart, Inc.

Other Identifiers

6084

Identifier Type: -

Identifier Source: org_study_id